The mixed leukocyte culture (MLC) and cell mediated lympholysis (CML) tests are used as in vitro models of in vivo allograft reactions. In MLC cells of one individual respond by proliferation primarily as they recognize foreign LD antigens determined by the major histocompatibility complex (MHC) on the stimulating cells of a second individual. In CML tests, cytotoxic T lymphocytes that are generated in MLC lyse target cells carrying the same MHC SD antigens that were present on the stimulating cells in MLC. The MHC LD and SD antigens are determined by genetically separable genes; the preferential activation of MLC and CML responses by these two antigenic systems respectively is based on the differential reactivity of two T cell subpopulations: the response of the proliferating T helper cell to the LD antigens enhances the development of cytotoxic T lymphocytes directed at the SD antigens in CML. It appears that LD disparity is predictive of the fate of kidney and skin allografts. This research application proposes to investigate further: (1) new rapid assays of LD determinants to gain a greater understanding of the immunogenetics of these systems and for use in donor-recipient pairing for transplantation; (2) the relative roles of MHC LD and SD antigens in MLC and CML, their interaction in terms of the enhancement of CML and the roles of these antigens in induction of tolerance and memory, (3) the above questions with respect to "secondary type" responses both after in vivo and in vitro sensitization, (4) cellular events as they relate to these various reactions, and (5) in vivo studies both in experimental species and in man to study the applicability of the in vitro findings.